tbuckley/cabot-search huggingface dataset:
Modified Biodegradation Behavior Induced Beneficial Microenvironments for Bone Regeneration by Low Addition of Gadolinium in Zinc (Adv. Healthcare Mater. 21/2022)
Authors: Hongtao Yang, Bo Jia, Xinhua Qu, Kerong Dai, Yufeng Zheng
Journal: Advanced Healthcare Materials (2022)

Biodegradable Materials In article 2201184 by Yufeng Zheng and co-workers, trace amounts of gadolinium are used to modify the biodegradation behavior of zinc via refinement of the intrinsic microstructure. As a result, a Zn-0.4Gd alloy implant generates beneficial microenvironments for bone regeneration by fulfilling the favorable biological role of zinc, contributing to improved osteogenesis and osseointegration.
Reinforced Hyaluronic Acid‐Based Matrices Promote 3D Neuronal Network Formation (Adv. Healthcare Mater. 21/2022)
Authors: Dieter Janzen, Ezgi Bakirci, Jessica Faber, Mateo Andrade Mier, Julia Hauptstein, Arindam Pal, Leonard Forster, Jonas Hazur, Aldo R. Boccaccini, Rainer Detsch, Jörg Teßmar, Silvia Budday, Torsten Blunk, Paul D. Dalton, Carmen Villmann
Journal: Advanced Healthcare Materials (2022)

Cortical Neurons In article 2201826 by Carmen Villmann and coworkers, box shaped poly(ɛ-caprolactone) frames made via melt electrowriting are used to reinforce hydrogels (back). The foreground shows the immunocytochemical image of a cortical neuron cocultured with astrocytes in HA-SH (neuron-MAP2 green; synaptophysin-magenta; DAPI blue).
First Nerve‐Related Immunoprobe for Guidance of Renal Denervation through Colocalization of NIR‐II and Photoacoustic Bioimaging (Adv. Healthcare Mater. 21/2022)
Authors: Shi Yibing, Tang Minna, Zhang Sidi, Hu Chenchen, Li Cheng, Li Quanxiao, Huang Keke, Song Wenping, Li Zhixing, Li Wenshu, Yang Zhenlin, Wu Yanling, Li Fuyou, Hu Jialu, Ying Tianlei
Journal: Advanced Healthcare Materials (2022)

Photoacoustic Imaging In the article 2201212, Li Fuyou, Hu Jialu, Ying Tianlei, and co-workers combine NIR-II and photoacoustic bioimaging systems based on a dye-modified anti-tyrosine-hydroxylase antibody (TH-ICGM) to illustrate the peritoneal sympathetic nerve-related region and provide 3D coordinates of procedure position for renal denervation. As the first nerve-related NIR-II immunoprobe, TH-ICGM has great clinical potential for assistance in nerve-related interventions.
Bispecific antibodies targeting CD40 and tumor-associated antigens promote cross-priming of T cells resulting in an antitumor response superior to monospecific antibodies
Authors: Karin Hägerbrand, Laura Varas, Adnan Deronic, Barnabas Nyesiga, Anette Sundstedt, Lill Ljung, Christina Sakellariou, Doreen Werchau, Mia Thagesson, David Gomez Jimenez, Lennart Greiff, Mona Celander, Kristine Smedenfors, Anna Rosén, Deniz Bölükbas, Fredrika Carlsson, Mattias Levin, Anna Säll, Laura von Schantz, Malin Lindstedt, Peter Ellmark
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Indications with poor T-cell infiltration or deficiencies in T-cell priming and associated unresponsiveness to established immunotherapies represent an unmet medical need in oncology. CD40-targeting therapies designed to enhance antigen presentation, generate new tumor-specific T cells, and activate tumor-infiltrating myeloid cells to remodel the tumor microenvironment, represent a promising opportunity to meet this need. In this study, we present the first in vivo data supporting a role for tumor-associated antigen (TAA)-mediated uptake and cross-presentation of tumor antigens to enhance tumor-specific T-cell priming using CD40×TAA bispecific antibodies, a concept we named Neo-X-Prime. Methods Bispecific antibodies targeting CD40 and either of two cell-surface expressed TAA, carcinoembryonic antigen-related cell adhesion molecule 5 (CEA) or epithelial cell adhesion molecule (EpCAM), were developed in a tetravalent format. TAA-conditional CD40 agonism, activation of tumor-infiltrating immune cells, antitumor efficacy and the role of delivery of tumor-derived material such as extracellular vesicles, tumor debris and exosomes by the CD40×TAA bispecific antibodies were demonstrated in vitro using primary human and murine cells and in vivo using human CD40 transgenic mice with different tumor models. Results The results showed that the CD40×TAA bispecific antibodies induced TAA-conditional CD40 activation both in vitro and in vivo. Further, it was demonstrated in vitro that they induced clustering of tumor debris and CD40-expressing cells in a dose-dependent manner and superior T-cell priming when added to dendritic cells (DC), ovalbumin (OVA)-specific T cells and OVA-containing tumor debris or exosomes. The antitumor activity of the Neo-X-Prime bispecific antibodies was demonstrated to be significantly superior to the monospecific CD40 antibody, and the resulting T-cell dependent antitumor immunity was directed to tumor antigens other than the TAA used for targeting (EpCAM). Conclusions The data presented herein support the hypothesis that CD40×TAA bispecific antibodies can engage tumor-derived vesicles containing tumor neoantigens to myeloid cells such as DCs resulting in an improved DC-mediated cross-priming of tumor-specific CD8 + T cells. Thus, this principle may offer therapeutics strategies to enhance tumor-specific T-cell immunity and associated clinical benefit in indications characterized by poor T-cell infiltration or deficiencies in T-cell priming.
Cardiac Development in the Presence of Cadmium: An <i>in Vitro</i> Study Using Human Embryonic Stem Cells and Cardiac Organoids
Authors: Xian Wu, Yichang Chen, Anthony Luz, Guang Hu, Erik J. Tokar
Journal: Environmental Health Perspectives (2022)

Background: Exposure to cadmium (Cd) is associated with cardiovascular diseases. Maternal Cd exposure is a significant risk factor for congenital heart disease. However, mechanisms of Cd on developmental cardiotoxicity are not well defined. Objectives: We evaluated the effects of Cd on the different stages (mesoderm, cardiac induction, cardiac function) of cardiac development using an early embryo development in vitro model and two- or three-dimensional (2- or 3D) cardiomyocyte and cardiac organoid formation models mimicking early cardiac development. Methods: Embryonic stem cells (ESCs) form 3D aggregates, called embryoid bodies, that recapitulate events involved with early embryogenesis (e.g., germ layer formation). This model was used for early germ layer formation and signaling pathway identification. The 2D cardiomyocyte differentiation from the NKX2-5eGFP/w human ESCs model was used to explore the effects of Cd exposure on cardiomyocyte formation and to model mesoderm differentiation and cardiac induction, allowing us to explore different developmental windows of Cd toxicity. The 3D cardiac organoid model was used in evaluating the effects of Cd exposure on contractility and cardiac development. Results: Cd (0.6μM; 110 ppb) lowered the differentiation of embryoid bodies to mesoderm via suppression of Wnt/β-catenin–signaling pathways. During early mesoderm induction, the mesoderm-associated transcription factors MESP1 and EOMES showed a transient up-regulation, which decreased later in the cardiac induction stage. Cd (0.15μM) lowered mesoderm formation and cardiac induction through suppression of the transcription factors and mesoderm marker genes HAND1, SNAI2, HOPX, and the cardiac-specific genes NKX2-5, GATA4, troponin T, and alpha-actinin. In addition, Cd-induced histone modifications for both gene activation (H3K4me3) and repression (H3K27me3), which play vital roles in regulating mesoderm commitment markers. The effects of Cd inhibition on cardiomyocyte differentiation were confirmed in 3D cardiac organoids. Discussion: In conclusion, using a human ESC-derived 2D/3D in vitro differentiation model system and cardiac organoids, we demonstrated that low-dose Cd suppressed mesoderm formation through mesoderm gene histone modification, thus inhibiting cardiomyocyte differentiation and cardiac induction. The studies provide valuable insights into cellular events and molecular mechanisms associated with Cd-induced congenital heart disease. https://doi.org/10.1289/EHP11208
The effect of colpectomy on lower urinary tract function in transgender men
Authors: Freek P. W. de Rooij, Brechje L. Ronkes, Freek A. Groenman, Mark-Bram Bouman, Jakko A. Nieuwenhuijzen, R. Jeroen A. van Moorselaar, Garry L. S. Pigot
Journal: International Journal of Transgender Health (2022)

Background: In transgender men, effects of colpectomy on voiding function are unknown, except for the incidence rates of urinary tract infections and urinary retention.Aims: To provide insight into the effect of colpectomy on Lower Urinary Tract Function (LUTF) in transgender men.Methods: A retrospective chart review was conducted among transgender men who underwent colpectomy between January 2018 and October 2020. Primary outcomes were objective and subjective changes in voiding. Secondary outcomes were transurethral catheterization length and the need for clean intermittent self-catheterization (CISC).Results: Of 132 men, 89 (67%) underwent Robot-assisted Laparoscopic Colpectomy (RaLC) and 43 (33%) Vaginal Colpectomy (VC). Maximum flow rate on uroflowmetry decreased following RaLC (mean of 29.1 vs. 38.3 mL/s, p = 0.002) and VC (mean of 29.2 vs. 40.3 mL/s, p < 0.001) after a median of four months postoperatively. An increase in total International Prostate Symptom Score was seen more frequently following VC compared to RaLC. Subjective changes were indicated by 39%, more often by men who underwent VC, of which the majority improved during the first months postoperatively. Trial without catheter (TWOC) on the first postoperative day was more successful after RaLC (79/89, 89%) than VC (24/43, 56%). Secondary TWOC was successful in 22/132 (17%) patients after a median of eight days postoperatively. In 5/132 (4%) men (three VC and two RaLC), temporary CISC was necessary for a period ranging from 5 to 21 days. The last 2/132 (2%) men after RaLC were still performing CISC at end of follow-up. Eventually, 5% (two VC and four RaLC) had to refrain from genital gender-affirming surgery with urethral lengthening due to voiding dysfunction.Discussion: After colpectomy, most objective and subjective worsening in LUTF is of a temporary nature, however, 5% had to refrain from genital gender-affirming surgery with urethral lengthening due to persistent voiding dysfunction, despite the desire to void while standing.
Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus
Authors: Afshan Saleem, Aamer Ikram, Evgenia Dikareva, Emilia Lahtinen, Dollwin Matharu, Anne-Maria Pajari, Willem M. de Vos, Fariha Hasan, Anne Salonen, Ching Jian
Journal: Gut Microbes (2022)

Biogeographic variations in the gut microbiota are pivotal to understanding the global pattern of host–microbiota interactions in prevalent lifestyle-related diseases. Pakistani adults, having an exceptionally high prevalence of type 2 diabetes mellitus (T2D), are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by bacterial 16S ribosomal RNA gene and fungal internal transcribed spacer (ITS) region amplicon sequencing and eubacterial qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide-binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis of the bacterial microbiota. Overall, urbanized Pakistanis' gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations, e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for a more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.
Noninvasive Respiratory Support for Adults with Acute Respiratory Failure
Authors: Laveena Munshi, Jordi Mancebo, Laurent J. Brochard
Journal: New England Journal of Medicine (2022)

Noninvasive respiratory support can be useful for cardiogenic pulmonary edema and COPD exacerbations. For other conditions, its benefits need to be balanced against the potential harms of delaying intubation.
Early Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years
Authors: Frank H. Bloomfield, Yannan Jiang, Jane E. Harding, Caroline A. Crowther, Barbara E. Cormack
Journal: New England Journal of Medicine (2022)

Whether higher parenteral amino acid intake improves outcomes in infants with extremely low birth weight is unclear.In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned infants with birth weights of less than 1000 g at 8 neonatal intensive care units to receive amino acids at a dose of 1 g per day (intervention group) or placebo in addition to usual nutrition for the first 5 days after birth. The primary outcome was survival free from neurodisability as assessed with the Bayley Scales of Infant and Toddler Development and neurologic examination at 2 years, corrected for gestational age at birth. Secondary outcomes were the components of the primary outcome as well as the presence or absence of neonatal disorders, the rate of growth, and nutritional intake.We enrolled 434 infants (217 per group) in this trial. Survival free from neurodisability was observed in 97 of 203 children (47.8%) in the intervention group and in 102 of 205 (49.8%) in the placebo group (adjusted relative risk, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P = 0.56). Death before the age of 2 years occurred in 39 of 217 children (18.0%) in the intervention group and 42 of 217 (19.4%) in the placebo group (adjusted relative risk, 0.93; 95% CI, 0.63 to 1.36); neurodisability occurred in 67 of 164 children (40.9%) in the intervention group and 61 of 163 (37.4%) in the placebo group (adjusted relative risk, 1.16; 95% CI, 0.90 to 1.50). Neurodisability was moderate to severe in 27 children (16.5%) in the intervention group and 14 (8.6%) in the placebo group (adjusted relative risk, 1.95; 95% CI, 1.09 to 3.48). More children in the intervention group than in the placebo group had patent ductus arteriosus (adjusted relative risk, 1.65; 95% CI, 1.11 to 2.46). In a post hoc analysis, refeeding syndrome occurred in 42 of 172 children in the intervention group and 26 of 166 in the placebo group (adjusted relative risk, 1.64; 95% CI, 1.09 to 2.47). Eight serious adverse events occurred.In infants with extremely low birth weight, extra parenteral amino acids at a dose of 1 g per day for 5 days after birth did not increase the number who survived free from neurodisability at 2 years. (Funded by the New Zealand Health Research Council and others; ProVIDe Australian New Zealand Clinical Trials Registry number, ACTRN12612001084875.).
A Shear Decline
Authors: Marla Lipsyc-Sharf, Nathan T. Connell, John W. Ostrominski, Bruce D. Levy, Joseph Loscalzo
Journal: New England Journal of Medicine (2022)

A 59-year-old man presented with a 3-week history of fatigue, light-headedness, and bifrontal headache. Two weeks earlier he had had watery diarrhea, including one episode of hematochezia, for 5 days.
Climate, Pollution, and Children’s Health
Authors: Kari Nadeau, Frederica Perera, Renee N. Salas, Caren G. Solomon
Journal: New England Journal of Medicine (2022)

Based on a Review Article by Drs. Frederica Perera and Kari Nadeau (Climate Change, Fossil-Fuel Pollution, and Children's Health, in the June 16, 2022, issue), this instructional video focuses on five key ways in which fossil fuels, air pollution, and climate change are creating a long-lasting negative impact on infant and children's health: extreme heat, climate-intensified events, changes in air quality, disruptions in food and water supply, and changes in vector ecology. Physicians play an important role in caring for children and pregnant persons affected by these changes. Physicians also can spread awareness of climate change and engage in advocacy to improve health and equity.
Psilocybin in Treatment-Resistant Depression
Authors: Bertha K. Madras
Journal: New England Journal of Medicine (2022)

Depression ranks first among psychiatric disorders that dominate the global burden of disease, posing a substantial personal strain and economic drain on nations.1 At least 30 drugs are Food and Drug Administration (FDA)–approved to treat depression,2 yet a systematic review and meta-analysis of 22 antidepressants concluded that although they were more effective than placebo in adults with major depressive disorder, effect sizes were mostly modest and tempered by an array of side effects.3 Because medicine abhors a therapeutic vacuum, the hallucinogens (psychedelic agents) psilocybin and lysergic acid diethylamide (LSD) are being revisited as potential candidate medications decades after their demise in . . .
Are We Too Reliant on Radiation Therapy for Children with Hodgkin’s Lymphoma?
Authors: Mark Roschewski, Catherine M. Bollard
Journal: New England Journal of Medicine (2022)

The treatment of Hodgkin's lymphoma is a success story that highlights our ability to cure cancer in advanced stages and when first-line therapy fails. Current goals focus on improving cure rates while mitigating the risk of long-term toxic effects that emerge during therapy and late effects that manifest after decades. Second cancers and cardiovascular complications are late effects that cause disease and death in patients who survived the initial cancer, but they may be relegated to secondary importance as compared with short-term disease control. Yet, the risk of second cancers continues to increase for at least 40 years after therapy, . . .
Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin’s Lymphoma
Authors: Sharon M. Castellino, Qinglin Pei, Susan K. Parsons, David Hodgson, Kathleen McCarten, Terzah Horton, Steve Cho, Yue Wu, Angela Punnett, Hema Dave, Tara O. Henderson, Bradford S. Hoppe, Anne-Marie Charpentier, Frank G. Keller, Kara M. Kelly
Journal: New England Journal of Medicine (2022)

In adults with advanced-stage Hodgkin's lymphoma, the CD30-directed antibody–drug conjugate brentuximab vedotin combined with multiagent chemotherapy has been shown to have greater efficacy, but also more toxic effects, than chemotherapy alone. The efficacy of this targeted therapy approach in children and adolescents with Hodgkin's lymphoma is unclear.
The Zollinger–Ellison Syndrome
Authors: Quentin Binet, Ivan Borbath
Journal: New England Journal of Medicine (2022)

A 75-year-old man presented with epigastric pain, diarrhea, and weight loss. Endoscopy revealed severe esophagitis, antral erosions, and duodenal ulcers. A fasting gastrin level was above 1000 pg per milliliter.
Parenteral Protein in Extremely Preterm Infants — More Is Not Better
Authors: Camilia R. Martin
Journal: New England Journal of Medicine (2022)

In utero transfer of nutrients to the fetus is critical for multiple organ development. The fetal accretion of nutrients is efficient, precisely regulated, and tailored throughout gestation. Premature delivery abruptly interrupts this process. Insufficient nutrient replacement early in the postnatal period puts the preterm infant at risk for nutrient deficits and health complications linked to restricted nutrition. Currently, the generally accepted goal for nutritional management of the preterm infant is to mimic the healthy fetus's nutrient delivery and growth rates. However, doing so does not account for the competing external factors that the critically ill preterm infant is exposed to . . .
Is It Burnout or Depression? Expanding Efforts to Improve Physician Well-Being
Authors: Srijan Sen
Journal: New England Journal of Medicine (2022)

Interview with Dr. Srijan Sen on the current emphasis on distinguishing burnout from depression and possible unintended consequences for physician well-being. (06:31)Download The current framing of physician burnout perpetuates misunderstandings and stigma associated with depression and deters us from fully utilizing the tools that can prevent and treat depression.
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
Authors: Guy M. Goodwin, Scott T. Aaronson, Oscar Alvarez, Peter C. Arden, Annie Baker, James C. Bennett, Catherine Bird, Renske E. Blom, Christine Brennan, Donna Brusch, Lisa Burke, Kete Campbell-Coker, Robin Carhart-Harris, Joseph Cattell, Aster Daniel, Charles DeBattista, Boadie W. Dunlop, Katherine Eisen, David Feifel, MacKenzie Forbes, Hannah M. Haumann, David J. Hellerstein, Astrid I. Hoppe, Muhammad I. Husain, Luke A. Jelen, Jeanine Kamphuis, Julie Kawasaki, John R. Kelly, Richard E. Key, Ronit Kishon, Stephanie Knatz Peck, Gemma Knight, Martijn H.B. Koolen, Melanie Lean, Rasmus W. Licht, Jessica L. Maples-Keller, Jan Mars, Lindsey Marwood, Martin C. McElhiney, Tammy L. Miller, Arvin Mirow, Sunil Mistry, Tanja Mletzko-Crowe, Liam N. Modlin, René E. Nielsen, Elizabeth M. Nielson, Sjoerd R. Offerhaus, Veronica O’Keane, Tomáš Páleníček, David Printz, Marleen C. Rademaker, Aumer van Reemst, Frederick Reinholdt, Dimitris Repantis, James Rucker, Samuel Rudow, Simon Ruffell, A. John Rush, Robert A. Schoevers, Mathieu Seynaeve, Samantha Shao, Jair C. Soares, Metten Somers, Susan C. Stansfield, Diane Sterling, Aaron Strockis, Joyce Tsai, Lucy Visser, Mourad Wahba, Samuel Williams, Allan H. Young, Paula Ywema, Sidney Zisook, Ekaterina Malievskaia
Journal: New England Journal of Medicine (2022)

In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery–Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).